Companion Animal Medical Guidelines – Urinary Tract
These guidelines are based on the International Society for Companion Animal Infectious Diseases (ISCAID) guidelines for the diagnosis and management of bacterial urinary tract infections in dogs and cats, with some changes based on Australian literature – especially the review which is summarised below.
Sporadic urinary tract infections
Previously called uncomplicated, sporadic bacterial infection of the bladder in an otherwise healthy animal with no underlying systemic, anatomic, neurologic or functional problem. Uncomplicated cases are not recurrent and occur less than 3 times per year. In an animal has had an infection (with clinical signs) in the last 3 months, they should be approached like ‘recurrent cystitis.’ For cases with co-morbidities or 3 or more episodes per year see recommendations for recurrent urinary tract infections below.
DIAGNOSTICS
Urinalysis should be performed including measurement of specific gravity, urine dipstick and cytological examination of stained and unstained urine sediment. Leukocyte and nitrite results on dipsticks are not reliable for veterinary species so pyuria can only be diagnosed using cytology. Sediment analysis alone is inadequate for diagnosis because of problems in the variable quality of interpretation, stain contamination and false positive results from bacteriuria in the absence of clinical infection.
Culture
Aerobic culture and susceptibility testing is recommended for all cases to confirm the presence of infection, identify the presence of resistant bacteria that may not respond to initial therapy, to help differentiate reinfection from relapse and to provide information on the most common bacteria causing urinary tract infections in the local area and local susceptibility patterns. Urine for culture should always be collected by cystocentesis unless there is a specific contra-indication. Culture should always be performed in cats presenting with signs of FLUTD. No culture can be justified in dogs if there was no previous exposure to antimicrobials (i.e. in last 3 months) and if the pathogen and its susceptibility pattern is predictable.
TREATMENT
If it is unclear whether culture will be positive, consider giving pain relief (if there are signs of pain) and await culture results rather than starting empirical antimicrobials straight away (see delayed prescribing technique).
If empirical antimicrobials are indicated, initial therapy should consist of amoxycillin or trimethoprim / sulphonamide.
DURATION OF THERAPY
Recommended treatment length is 3-5 days.
Treatment of intact male dogs with no evidence of prostatitis or animals with comorbidities not involving the urinary tract (e.g. pets with clinical UTIthat receive immunosuppressives, are obese or have endocrinopathies) and with non-recurrent cystitis are included in the above recommendation.
There should be an adequate response to treatment within 48 hours (i.e. signs reduce/resolve) and if not, further investigation considered. DO NOT change antibiotics empirically (i.e. without culturing) if clinical signs persist.
Change antibiotics if initial culture results indicate resistance to empirical antimicrobial AND there is a lack of response. Do not change antibiotics if there was good clinical response (even if the bacteria are resistant in vitro).
If clinical signs resolve, follow up culture is NOT recommended
Recurrent urinary tract infections
Any infection that occurs in the presence of an anatomic or functional abnormalities or in an animal that has a comorbidity that predisposes to persistent infection, recurrent infection or treatment failure. Recurrent infections (3 or more episodes of infection during a 12-month period) can be further categorised as:
| Reinfection | Recurrence of infection within 6 months of cessation of previous, apparently successful treatment and isolation of a different microorganism |
| Relapse | Recurrence of infection within 6 months of cessation of previous, apparently successful treatment and isolation of the same microorganism |
| Refractory | Similar to a relapse except that it is characterised by persistently positive culture results during treatment |
Co-morbidities that should be considered:
- Endocrinopathy
- Kidney disease
- Obesity
- Abnormal vulvar conformation
- Congenital abnormalities of the urogenital tract (e.g. ectopic ureter, mesonephric duct abnormalities)
- Prostatic disease
- Bladder tumor
- Polypoid cystitis
- Urolithiasis
- Immunosuppressive therapy
- Rectal fistula
- Urinary incontinence/retention
DIAGNOSTICS
The same principles for diagnosis apply from uncomplicated infections. Presence of underlying factors should be investigated and client compliance with previous therapy ensured, especially in case of relapse. Consider whether the antimicrobial chosen is appropriate in dosing/dosing frequency to achieve adequate concentrations at the site of infection. Urine culture is always needed for ongoing management, antimicrobials should not be changed empirically.
TREATMENT
Treatment should be based on culture and susceptibility testing results. If required, empirical therapy can be initiated prior to results with amoxycillin or trimethoprim / sulphonamide. Preference should be given to drugs that are excreted in the urine in the active form (not macrolides).
Anecdotal evidence suggests that in mixed infections including Enterococcus spp., infection with this isolate will often resolve with effective treatment of other isolates, however ideally an antimicrobial that is effective against both pathogens should be selected. Note, there is no evidence that some drugs (ie clarithromycin) are effective at breaking down biofilms, these should be avoided as they are not excreted in the urine in active forms.
DURATION OF THERAPY
Treatment length may vary depending on the clinical signs/comorbidities; goal of treatment is clinical cure (i.e. no clinical signs) and no adverse effects (including antimicrobial resistance). Microbiological cure (i.e. negative culture) is desirable but not necessarily achievable.
Consider pain relief whilst awaiting culture results, in lieu to starting antimicrobials empirically straight away. If empirical therapy is started, first choice is as for sporadic cystitis
Short duration (3-5 days) should be considered, particularly if infection appears to be a reinfection (not relapse/persistence) and/or the animal has comorbidities that relate to organs other than the urinary tract
Recommendation for longer courses has now shortened to 7-14 days (used to be 4 weeks); these to be considered if there are urinary tract abnormalities (e.g. bladder mucosa abnormalities)
If there is likely tissue involvement (e.g. bladder wall mucosa infection, TCC) then antimicrobial type and dosing needs to achieve adequate concentration in tissue, i.e. amoxicillin-clavulanate is NOT recommended.
Culture during treatment not recommended if short duration of treatment chosen. Culture after 5-7 days is reasonable if there is a longer duration of treatment, but approach to culture result must be considered. Positive cultures indicate the need for evaluation of compliance and further diagnostic testing, to determine why the bacterium has not been eliminated, not simply a change in antimicrobial, particularly if clinical cure has been documented. Negative results could be used to help determine when to stop therapy if a long course of treatment is being used, but are not a guarantee of microbiological cure. Culture of urine specimens, ideally collected by cystocentesis, can be considered 5–7 days after cessation of antimicrobials in animals where clinical cure is documented. However, this should be used as part of the diagnostic process to help differentiate relapse, re-infection and persistent infection, and to guide potential future diagnostic testing, not as an indication of a need to treat. The presence of bacteriuria post-treatment should be approached as described under ‘Subclinical bacteri-uria’. If client compliance is deemed to have been adequate, referral to a specialist should be considered to explore reasons for microbial persistence or rapid re-infection.
Subclinical bacteriuria
Evidence of positive urine culture in the absence of clinical signs. Please note that urinalysis results (pyuria, haematuria, bacteriuria) may not correlate with culture results and poorly correlate with clinical signs. Attempts must be made to differentiate between SBU and clinical UTI based on history and clinical examination findings (not clinicopathological findings, e.g. urinalysis).
A patient that has pyuria and a positive culture but no clinical signs is considered to have SBU, not clinical infection.
A patient with heavy growth of bacteria on culture, but no clinical signs is considered to have SBU, not clinical infection.
SBU is a common finding particularly in animals with comorbidities (15-74% of these can have SBU), but may also happen in otherwise healthy dogs/cats (up to 13% of these can have SBU). SBU may not have clinical consequence, i.e. animals with SBU may not be at high risk of developing clinical disease however studies are limited. In people there is considerable evidence that treatment of asymptomatic bacteriuria (the equivalent of SBU in people) should not include antibiotics.
Culture of urine is NOT recommended when the animal does not have clinical signs (and there is no intention to treat), even if the animal has co-morbidities that predispose to bacteriuria (e.g. Diabetes Mellitus)
Retesting to assess whether SBU resolves is NOT recommended
TREATMENT
Treatment of SBU with antimicrobials is discouraged, even if there is evidence of pyuria or the isolated organism is multi-drug resistant. If it is unclear whether the animal has SBU or clinical UTI a short course of treatment (3-5 days, as for sporadic cystitis) is recommended – if there is no discernable clinical improvement further treatment is discouraged.
In rare circumstances, treatment of SBU may be considered if there is concern of high risk of ascending or systemic infections. By extrapolation of data from humans, not many animals may be at risk of developing ascending or systemic infections when SBU is present.
In animals that cannot display clinical signs (e.g. paralysed) judgement must be made whether treatment is indicated.
If Corynebacterium urealyticum or Staphylococci are isolated short course treatment may be considered because of their associations with encrusting cystitis and struvite urolith formation, respectively. Because of the potential difficulties in treating these conditions, consideration of a single short course (3–5 days duration) of treatment, as per ‘Sporadic bacterial cystitis’, could be considered after confirming that bladder wall plaque or uroliths are not present. However, it is unknown whether this is a necessary or effective approach. Continued treatment of subclinical bacteriuria with these strains is likely not warranted.
There is currently no evidence that adjunctive treatment (e.g. cranberry extract) is effective but there is no contraindication to the use of supplements that are known to be safe.
If an animal subsequently develops clinical UTI or pyelonephritis, it must not be assumed that this is caused by the SBU strain. Approach these cases is as mentioned in other categories (i.e. recurrent cystitis, pyelonephritis).
Pyelonephritis
DIAGNOSTICS
Definitive diagnosis of pyelonephritis is challenging. A diagnosis of acute pyelonephritis can be suspected based on positive aerobic bacterial urine culture when accompanied by systemic signs such as fever, lethargy, and/or polyuria/polydipsia; renal pain on abdominal palpation; laboratory findings of azotemia, cylindru- ria, and peripheral neutrophilia with or without left shift (in the absence of another identifiable cause). However, animals with acute pyelonephritis may be oliguric or anuric or have vague clinical signs.
Imaging findings such as renal pelvic dilation and/or blunting of the renal papilla on ultrasound examination may be noted, but are non-specific. Care should be taken not to over-interpret the relevance of renal pelvic dilation, since it can be present in normal animals and those with other renal diseases.
Increased concentrations of biomarkers such as serum creatinine or serum symmetric dimethylarginine (SDMA) can also support the presence of renal injury in association with bacteriuria, but are indicators of glomerular filtration rate and are not specific for bacterial pyelonephritis as the cause of kidney injury.
Culture and susceptibility testing should always be performed. Cystocentesis specimens should be used for culture. Obtaining a urine specimen for cytology and culture by pyelocentesis should be considered, particularly if results of culture of a cystocentesis specimen are negative, or when a cystocentesis specimen cannot be obtained. Blood cultures are recommended at the same time as urine cultures in immunosuppressed or febrile animals. Interpretation of susceptibility data should be based on antimicrobial breakpoints for serum rather than urine drug concentrations. It is important that culture specimen submissions indicate that pyelonephritis is suspected to ensure that urine breakpoints are not applied. If multiple organisms are isolated from urine, the suspected relative relevance of these should be considered. This assessment would include the bacterial species and colony counts. Evaluation for leptospirosis should be considered in culture-negative dogs by use of serological testing and PCR.
TREATMENT
Serum/soft tissue concentrations of the antimicrobial are the key determinant to potential drug efficacy rather than urine concentrations (i.e. chose antimicrobials that ‘reach’ tissue). Initial (empirical drugs) should be effective against Enterobacteriaceae (e.g. E. coli) e.g consider fluoroquinolones. If the animal is clinical unwell (dehydrated, anorexic, lethargic) consider parenteral administration
Review antimicrobial therapy when culture results are available (i.e. consider de-escalation if 2 antimicrobials used; consider change if resistance in vitro and no clinical response; if there is clinical response then same antimicrobial therapy may be continued despite in vitro resistance, if response is not explained by other treatment factors (e.g. fluids, pain relief).
Consult with specialist if multidrug resistance is encountered.
If there is no appropriate response to treatment within 72 hours of therapy then diagnosis needs to be re-considered, e.g. it could be possible that there is other disease explaining the signs and concurrent subclinical bacteriuria.
DURATION OF THERAPY
Treatment length recommendation is 10-14 days. Physical examination, clinicopathological examination (e.g. CBC/biochem) and urine culture 1-2 weeks after cessation of therapy.
However, if clinical signs and azotemia have resolved, consideration has to be given to the clinical relevance of microbiological failure, as it may represent subclinical bacteriuria and not indicate a need for treatment. Re-isolation of the same bacterial species as that identified initially should stimulate consideration of reasons for potential persistence, including antimicrobial resistance, urolithiasis, anatomic defects or immune deficiency. Management of positive urine cultures in animals that have responded clinically and hematologically should be as per ‘Subclinical bacteriuria’.
Indwelling urinary catheters
Proper (aseptic) catheter placement and maintenance are critical. Open collection systems should not be used. Urinary catheters should be inspected regularly for any problems that could predispose to infection (e.g. breaks, gross fecal contamination). Routine catheter replacement to prevent bacteriuria or cystitis is not recommended.The duration of catheterisation should be as short as possible. The need for a urinary catheter should be re-evaluated regularly (at least daily, if not more frequently) and catheters should be removed as soon as they are deemed unnecessary. In humans, prompt catheter removal is considered one of the most, if not the most, important infection prevention tool. Intermittent catheterisation could be considered in selected patients where repeated atraumatic catheterisation is possible.
Routine cytological evaluation of urine is not recommended for detection of bacteriuria or bacterial cystitis. Pyuria, hematuria or cytological evidence of bacteria can occur in the absence of cystitis. Urine culture is not recommended in the absence of clinical signs consistent with cystitis, pyelonephritis, or where the bladder is being investigated as a potential source of systemic infection.
Treatment of bacteriuria in the absence of clinical evidence of cystitis or pyelonephritis is not recommended. Prophylactic antimicrobial therapy for prevention of cystitis in catheterised animals is not indicated. The use of methenamine as a urinary antiseptic is not recommended. There is currently no evidence that cranberry extracts or probiotics for prevention of catheter-associated bacterial cystitis are effective, but there is no contraindication to the use of treatments and supplements that are known to be safe. Infusion of biocides or antimicrobials into the bladder via the catheter is not recommended.
Catheter removal or replacement is not required in animals with subclinical bacteriuria, considering bacteriuria is common and not predictive of cystitis. Further, changing catheters might increase the risk of infection from contamination or trauma during catheter replacement. While urinary catheters coated with antibacterial substances such as silverorchlorhexidine may reduce bacterial colonisation of the catheter and biofilm formation, there is inadequate clinical evidence to support their use for prevention of catheter-associated bacterial cystitis.
Management of patients after urinary catheter removal
Culture of the catheter tip at the time of catheter removal is not recommended. Colonisation of catheter tips is common (e.g. up to 42–56% in dogs and cats) and catheter tip culture results are not predictive of development of cystitis. Routine urine culture after catheter removal is not recommended; however, if specific aspects about the case indicate a need for culture, cystocentesis should be performed, whenever possible. If clinical signs of cystitis develop after catheter removal, diagnosis should be performed as per ‘Sporadic bacterial cystitis’ (i.e. using cystocentesis, if possible).
There is no indication for routine (prophylactic) antimicrobial treatment following urinary catheter removal in an animal with no evidence of cystitis.
Catheterised animals with clinical signs of cystitis
Bacterial cystitis should be suspected in catheterised animals that develop lower urinary tract signs, yet such patients may not be easily identified (e.g. dogs with indwelling catheters for management of intervertebral disc disease). As such, infection should be suspected in all cases of fever of unknown origin or bacteremia with an unknown focus. A sudden change in the character of the urine (e.g. odor, gross appearance) should prompt consideration of whether bacterial cystitis has developed. These changes are not necessarily indicative of bacterial infection and should prompt further investigation, not necessarily treatment. Urine culture should always be performed if bacterial cystitis or bacteraemia is suspected. If catheterisation is still required and signs of bacterial cystitis are present, the recommended approach is to remove the catheter, collect urine by cystocentesis, then place a new catheter. If this is not possible, the catheter should be removed, a new catheter placed and urine collected from the new catheter for culture. The first 3–5 mL of urine collected should be discarded before collecting the urine specimen for culture.
Culture of the catheter tip at the time of removal is not recommended because of the potential for colonisation of the catheter with various bacteria, as well as contamination during catheter removal.
Urine culture should never be performed on urine from the collection bag or other part of the urine collection system. Treatment of catheter-associated bacterial cystitis is more likely to be successful if the catheter can be removed. The cost-benefit of removing or retaining the catheter should be considered in the context of management of the infection and the patient’s underlying disease condition. In uncommon situations where treatment is indicated, antimicrobials should be selected as per ‘Sporadic bacterial cystitis’. After clinically-apparent resolution of catheter-associated bacterial cystitis, if the catheter cannot be removed, it should be replaced with a new catheter, since colonisation of the catheter is likely, even with clinically successful treatment.
Bacterial prostatitis
Consider bacterial prostatitis in every entire male dog.
Various bacteria can be involved, including a range of Gram-negative (e.g. E. coli, Klebsiella, Pseudomonas, Pasteurella) and Gram-positive (e.g. Streptococcus, Staphylococcus) species. Brucella canis is a potentially important zoonotic pathogen that can also be involved.
DIAGNOSIS
An investigation for underlying bacterial prostatitis should be performed in every intact male dog diagnosed with bacteriuria or bacterial cystitis.
A full diagnostic examination, including physical examination, per rectum palpation of the prostate, complete blood cell count, biochemical profile, urinalysis and urine culture (collected by cystocentesis) should be considered. Ultrasonographic evaluation of the prostate is recommended to characterise the size and structure of the prostate, to identify changes consistent with neoplasia (e.g. mineralisation) or abscessation. Cytological examination and aerobic bacterial culture should be performed on the third fraction of the ejaculate, fluid collected by urethral catheterisation or per-rectum prostatic massage, or prostatic fluid collected by fine needle aspiration. The latter is particularly helpful when there is strong suspicion for prostatitis and the urine culture is negative for bacterial growth. Collection of ejaculated prostatic fluid may not be possible in dogs with acute prostatitis because of pain but may be successful in some cases, particularly with methods that can include sedation and analgesia. Oftentimes, a positive urine culture combined with clinical signs and ultrasonographic findings are used to make the diagnosis of bacterial prostatitis. Culture of ultrasound-guided aspirates or prostatic tissue biopsies can be more specific than ejaculate fluid or fluid collected by prostatic lavage as contamination is less likely. These techniques should be considered when equipment and expertise are available. Prostatic aspirates and biopsies should also be submitted for cytological or histopathological examination in cases of concurrent neoplasia. Culture of urine collected by cystocentesis can provide a reasonable estimate of the causative agent of prostatitis but discordance between urine and prostatic fluid culture results can occur. Mycoplasma and Ureaplasma culture could be considered but is of low yield because the incidence of infections caused by these organisms is low. Quantitative culture of prostatic fluid can be performed; however, clear data are lacking for interpretation. Prostatic fluid is not expected to be sterile because of the potential for normal reflux of bacteria into the prostate, as well as lower urinary tract contamination during ejaculation or prostatic lavage. Prostatic fluid CFU counts can be high (e.g. 100,000 CFU/mL) in healthy dogs. It has been suggested that a 2-log difference between prostatic and urine CFU counts is indicative of bacterial prostatitis, but objective data are lacking.
Isolation of Brucella canis at any level of growth is significant, but serological testing is recommended if B. canis infection is possible because of laboratory biosafety hazards associated with isolation of this bacterium and the potential for false negative cultures. Testing for B. canis should be performed in any dog that is intended to be used for breeding. Antimicrobial susceptibility breakpoints for serum, not urine, should be used because the concentration of the antimicrobial in the prostatic tissue is likely to most closely approximate that in the serum. However, not all antimicrobials penetrate the blood-prostate barrier equally, and this must be considered when selecting an appropriate antimicrobial.
TREATMENT
Prostatic abscesses should be drained because of the low likelihood of resolution with medical treatment alone. Surgical or ultrasound-guided percutaneous drainage can be per- formed. This should be performed after culture results are available, whenever possible, to facilitate proper peri-operative antimicrobial therapy. Concurrent with drainage, treatment as for chronic prostatitis should be administered. Empirical treatment should target Enterobacteriaceae. Administration of a veterinary fluoroquinolone should be considered while awaiting culture and susceptibility testing results, particularly if brucellosis is suspected.
Trimethoprim-sulfonamide has a spectrum of activity that includes a broad range of potential pathogens.
Clindamycin and macrolides can effectively penetrate the blood-prostate barrier, but should only be used based on culture and susceptibility test results, and not for empiric therapy because of lack of efficacy against Gram-negative bacteria. The blood-prostate barrier reduces the penetration of many drugs, such as penicillins, cephalosporins, aminoglycosides and tetracyclines. This barrier is typically considered to be less intact in acute prostatitis; however, these drugs should be avoided, regardless of in vitro susceptibility data, particularly in cases of chronic prostatitis. If a bacterial isolate that is resistant to fluoroquinolones, trimethoprim-sulfamethoxazole, clindamycin and chloram- phenicol is present, consultation with a theriogenologist, veterinary microbiologist, pharmacologist or internist with expertise in infectious diseases or urology is recommended. Ciprofloxacin should not be used because of the unpredictable bioavailability in dogs and relatively poor prostate penetration compared to enrofloxacin.
DURATION OF THERAPY
Four weeks is typically recommended for acute prostatitis, with 4–6 weeks for chronic disease. Shorter durations might be effective in acute cases that are castrated and where there is quick clinical response; however, objective data are lacking. A longer duration of treatment may be required in some chronic cases, particularly when abscessation is present or when castration is not performed. Castration should be recommended in dogs that are not intended for breeding. Castration does not alter the recommended antimicrobial drug choice or duration, but should be performed as early as is possible. Other medical approaches to control underlying prostatic disease should be considered (e.g. finasteride, androgen receptor antagonists or GnRH agonists). These approaches are less successful when intraprostatic cysts or abscesses are present. Ultrasonographic re-evaluation of prostatic size and internal architecture is advised in dogs 8–12 weeks after treatment.
When initial treatment has failed and antimicrobial resistance or other correctable factors such as client compliance have not been implicated as the cause, resolution of infection is unlikely. In such cases, castration is strongly recommended, if not performed initially. Poor initial response to therapy should lead to re-assessment of the diagnosis and if prostatitis is still suspected. Collection of ultrasound-guided fine needle aspirate of prostatic cyst fluid or prostatic tissue core biopsy for culture and cytology or histopathology should be considered, and/or a BRAF test if not already performed. If further testing is not possible and prostatitis is still suspected, empirical change to a different antimicrobial can be considered because ejaculate culture does not always correlate with prostatic cyst fluid or prostate tissue core biopsy culture. A drug from a different drug class should be chosen if an empirical change is made. In dogs with persistent prostatic abnormalities (e.g. prostatomegaly) but no clinical signs consistent with prostatitis, subsequent treatment should focus on treatment of episodes of cystitis that develop. This should be managed as described under ‘Sporadic bacterial cystitis or “Bacterial prostatitis”, with the goal being elimination of clinical signs.
Prostatic size should be monitored by ultrasound transrectal palpation. Culture of prostatic fluid or urine can be performed during the course of therapy, but is not recommended. Clinical response and monitoring of prostatic size/architecture are better indicators of whether treatment is successful. Semen quality improves with resolution of bacterial prostatitis in most cases.
The evidence
- Lekcharoensuk C, Osborne CA, Lulich JP. Epidemiologic study of risk factors for lower urinary tract diseases in cats. J Am Vet Med Assoc 2001;218:1429-1435.
- Mayer-Roenne B, Goldstein RE, Erb HN. Urinary tract infections in cats with hyperthyroidism, diabetes mellitus and chronic kidney disease. J Feline Med Surg 2007;9:124-132.
- Litster A, Moss S, Platell J, et al. Occult bacterial lower urinary tract infections in cats-urinalysis and culture findings. Vet Microbiol 2009;136:130-134.
- Barsanti JA, Shotts EB, Crowell WA, et al. Effect of therapy on susceptibility to urinary tract infection in male cats with indwelling urethral catheters. J Vet Intern Med 1992;6:64-70.